Postgraduate lecture to learn the basics for Evaluation of Seizures etiology

1. Evaluation of Seizure Etiology
By
Mohamed A. Tarek
FEBN

2. Agenda
• Seizure Evaluation
• Investigations
• Etiology
• Home message

3. Seizure Evaluation : Step 1
1- History …History ….History:
beginning with the question of whether a spell is
Truly epileptic ?
physiologic?
Psychogenic?
Paroxysmal , transient phenomenon?
• 2-we need to decide whether an epileptic seizure was caused by an acute insult ,
provoked by other triggers .
Or
related to a predisposition for recurrent, unprovoked seizures, defined as epilepsy .

4. Seizure Evaluation : Step 1

5. Seizure Evaluation : Step 2

6. Seizure Evaluation : Step 2

7. Algorithm for New onset seizure

8. Investigations
• CT and / or MRI brain Epilepsy Protocol
• MRA-MRV>>> if AVM is suspected
• EEG
• Complete blood cell count;
• Blood chemistry: including calcium, magnesium, and phosphate; thyroid-
stimulating hormone;
• Urine toxicology.
• A 12-lead ECG

9. Brain Imaging
•CT scan :
is often used as the first imaging modality because
of its ease of access and should be considered for
patients with new-onset seizures seen in the
emergency department to assess for an acute
brain insult, such as a stroke, bleed, or traumatic
injury .

10. Brain Imaging
• MRI brain (Epilepsy Protocol):
An epilepsy-protocol brain MRI differs from a typical MRI in that it includes thin 1-
to 3-mm slices without interslice gap and coronal fluid–attenuated inversion
recovery sequences, which offer additional sensitivity over standard-protocol
MRIs.

11. Hippocampal Sclerosis

12. Focal Cortical Dysplasia

13. Rasmussen Encephalitis

14. Ant . Choroidal a. infarction

15. HS vs Tumor

16. Cavernoma

17. Polymicrogyria

18. Nodular Heterotopia

19. Double Cortex

20. Post vascular injury

21. Post traumatic brain Injury

22. DNET
• Dysembryoplastic neuroepithelial tumor (DNET) in a
21-year-old man with temporal lobe epilepsy.
• A small simple variant DNET with intracortical cysts
(a–f: arrow) representing the glioneuronal element
is located in the right inferior temporal gyrus.
• Note also the small spatially separated cyst in the
hippocampal body (a–f: hollow arrow).
• No contrast enhancement or calcifications are
present in this patient (e–f)

23. Anaplastic astrocytoma
A 46-year-old man with new-onset status epilepticus.
Non-enhanced head CT (a) shows subtle hypo- density
in the splenium of the corpus callosum (arrow). Axial
FLAIR MR image (b) shows a high signal of the corpus
callosum lesion extending into the left occipital
parasagittal region (arrow) with diffusion restriction (c
arrow) and enhancement on gadolinium-enhanced T1-
weighted image (d arrow).
Biopsy revealed WHO grade III anaplastic astrocytoma

24. AVM

25. Herpes Encephalitis

26. Autoimmune limbic encephalitis

27. Hypothalamic Hamartoma

28. Important Hints
• Patients with a first seizure, who have an epileptogenic structural abnormality on brain
imaging and/or interictal epileptiform activity on EEG, have a greater than 60% risk of
recurrence after a first unprovoked seizure and are considered as having epilepsy >>>>
Those patients typically benefit from antiepileptic medication, which is also considered for
patients after a first nocturnal convulsion.
• Acute brain insults can have a risk of leading to late seizures in up to 20% of patients and do
not warrant prolonged seizure prophylaxis, even if the injury was associated with early
seizures or status.
• Exceptions are possibly a penetrating head trauma and herpes encephalitis, which are
associated with a 50% risk of developing epilepsy.

29. EEG
Emergency EEG is indicated for :
- Patients who do not have a timely recovery after a seizure.
- Have fluctuating mental status changes.
- Show a neurologic deficit that is not explained by the imaging findings.
-A routine EEG is insufficient to detect subclinical seizure activity, which is captured within
ü the first 30 minutes. >>> in only one-fourth of patients found to have subclinical seizures on
long-term monitoring
ü the first 2 hours. >>> in one-half of those patients.
ü 24- to 36-hour continuous recordings >>> The yield increases to greater than 90%

30. EEG
• There does appear to be a slightly higher yield of epileptiform abnormalities on
EEGs performed in patients within 24 to 48 hours of a new-onset seizure.
• Patients presenting with a provoked seizure should get at least an EEG and a
brain imaging study because not infrequently they are found to have a remote
structural abnormality or an EEG indicating a predisposition for generalized
seizures.

31. Seizure Evaluation
• Patients with established epilepsy may have several seizure types. The interview
should provide guidance for the patient to describe the seizures in his or her own
words, to characterize different seizure types associated with specific epilepsy
syndromes, or recognize that focal seizures often evolve from an aura to loss of
awareness and sometimes convulsions.
• For patients with epilepsy who continue to have seizures, we want to know if the
seizure was caused by some trigger or nonadherence to medication or is indicative of
an incomplete medication response requiring medication adjustment.
• Seizures may be seen mostly during certain times of the day or triggered by specific
situations, suggesting a form of rare reflex epilepsy.

32. Seizure Evaluation

33. Seizure Evaluation

34. Case
• A 31 year-old woman has a strange sense of familiarity (déjà
vu), then smacks her lips, rocks back and forth. She has no
awareness or memory of the event.
• Type of seizure :
a) Focal
b) Generalized

35. Case
• A 31 year-old woman has a strange sense of familiarity (déjà vu), then
smacks her lips, rocks back and forth. She has no awareness or
memory of the event.
Which category ?
a) Focal aware
b) Focal with impaired awareness
c) Focal to bilateral tonic clonic

36. case
• A 31 year-old woman has a strange sense of familiarity (déjà vu), then
smacks her lips, rocks back and forth. She has no awareness or memory of
the event.
Focal seizure type?
a)Non-motor onset cognitive
b)Non-motor onset autonomic
c)Non-motor onset emotional
d)motor onset automatism

37. Seizure Evaluation
•Epilepsy Syndromes :
The recognition of these syndromes is not only important for treatment
and prognosis, it also guides genetic evaluation because many of the
established epilepsy syndromes have a likely genetic etiology.

38. Seizure Evaluation
Epilepsy Syndromes

39. Epilepsy syndromes

40. Neonatal Epilepsy Syndromes

41. Neonatal Epilepsy Syndromes

42. Neonatal Epileptic Encephalopathy Syndromes

43. Burst Suppression in EME/EIEE
The background EEG is abnormal in all states, with a suppression-burst pattern. High voltage bursts
(150-300uV) of spikes or sharp and slow waves, lasting 1-3 seconds are seen with inter-burst intervals
of 3-5 seconds.

44. Otahara syndrome

45. Infantile Epilepsy Syndromes

46. MYOCLONIC EPILEPSY IN INFANCY
• Onset of myoclonic seizures: between the ages of 6 months and 2 years.
• Myoclonic seizures may be induced by photic stimulation in some patients, or by
sudden noise or touch in others.
• Infrequent febrile seizures may be seen in approximately 10% of patients.
• Seizures remit within 6 months to 5 years from onset but generalized tonic-clonic
seizures may be seen in teenage years in 10-20% of patients.
• Males are twice as likely to be affected as females.

47. MYOCLONIC EPILEPSY IN INFANCY

48. WEST Syndrome
• Triad of :
- Infantile spasms ( Flexor , Extensor or both)
- Psychomotor retardation or regression
- Specific EEG changes (Hypsarrythmia)
• Related to prenatal , Natal or postnatal insult
• Infants with Ohtahara syndrome or other early onset epilepsies
(typically with focal seizures) may evolve to have clinical and EEG
features of West syndrome after 3-4 months of age.
• Both sexes are affected, with a higher incidence in males.
William James west

49. WEST Syndrome

50. WEST Syndrome

51. Dravet Syndrome
(severe myoclonic epilepsy of infancy, SMEI)
• Very sensitive to increased temperature .
• typically presents in the first year of life in a normal child with
prolonged, febrile and afebrile, focal (usually hemiclonic) and
generalized tonic-clonic seizures.
• May have Myoclonic , Atypical Absence , Atonic seizures.
• The hemiconvulsive aspect usually alternates sides >>>characteristic of
this syndrome.
• 25% of Patients have seizures induced by visual stimuli.
• Seizures are usually intractable and from the second year of life children
demonstrate cognitive and behaviour impairments.
Charlotte Dravet

52. Dravet Syndrome

53. Childhood Epilepsy Syndromes

54. Benign childhood epilepsy with centrotemporal spikes
(BCECTS)(Rolandic Epilepsy)
• onset of seizures between 3 and 14 years (peak 8-9 years).
• Seizures usually resolve by age 13 years,but can occasionally occur up to age 18 years of age.
• The seizures are brief, hemifacial seizures that may evolve to a focal to bilateral tonic-clonic seizure if they occur nocturnally.
• Common characteristic features:
ü Unilateral somatosensory involvement
ü Speech arrest
ü Preservation of consciousness
ü Pooling of saliva
• Both sexes are affected.
• Antecedent, birth and neonatal history is normal. A history of febrile seizure (in 5-15%) may be seen.
• Development and cognition prior to onset of seizures is normal.

55. BECTS

56. Childhood Epilepsy with occipital Paroxysms
PANAYIOTOPOULOS SYNDROME
• onset of seizures between 1 and 14 years of age (majority between 3 and 6 years).
• Seizures are infrequent in most patients, with 25% having a single seizure (which may
be autonomic status epilepticus) and 50% having six seizures or less.
• Frequent seizures can occur in some patients.
• Focal autonomic seizures or autonomic status epilepticus , frequently with emesis.
• Seizures usually resolve by age 11-13 years.
• Both sexes are affected equally.
• Antecedent and birth history is normal.
• Development and cognition are normal.

57. PANAYIOTOPOULOS SYNDROME

58. Childhood Epilepsy with occipital Paroxysms
Gastaut type
• is a self-limiting childhood epilepsy with onset in later childhood. Seizures are usually easily controlled, and
remission of seizures occurs within 2-4 years from onset.
• onset of seizures between 15 months and 19 years of age (peak 8-9 years).
• Formed visual hallucinations or amaurosis followed by hemiclonic convulsions with post icteal migraine.
• Remission occurs in 50-60% of patients within 2-4 years after onset.
• A dramatic response to carbamazepine is seen in more than 90% of patients.
• Both sexes are equally affected.
• Antecedent and birth history is normal.
• Development and cognition is normal, although mild cognitive impairment has been described.

59. Childhood Epilepsy with occipital Paroxysms
Gastaut type

61. Childhood Absence Epilepsy
• is a genetic/idiopathic generalized epilepsy that should be considered in an otherwise normal child with multiple
daily absence seizures associated with 2.5 - 3.5 Hz generalized spike-and-wave.
• Absence seizures are provoked by hyperventilation.
• onset of frequent absence seizures between the ages of 2 to 12 years (peak 5-6 years).
• Both sexes are equally affected.
• Antecedent and birth history is normal.
• A previous history of febrile seizures may occur (seen in 15-20% of cases).
• Development and cognition are typically normal.
• Attention deficit hyperactivity disorder and learning difficulty may occur.
• Seizures are typically self-limiting.

62. Childhood Absence Epilepsy

63. EPILEPSY WITH EYELID MYOCLONIAS
Jeavons syndrome
• This syndrome (previously known as Jeavons syndrome) is characterized by daily eyelid
myoclonias with or without absences induced by eye closure and visual stimulation, seen in an
otherwise normal child.
• Absence seizures accompanied by brief, repetitive, often rhythmic, fast (4-6 Hz) myoclonic jerks of
the eyelids with simultaneous upward deviation of the eyeballs and extension of the head.
• Seizures are typically very brief (<6s in duration) and multiple seizures occur on a daily basis.
• Mostly awareness is retained

64. EPILEPSY WITH EYELID MYOCLONIAS
Jeavons syndrome

65. EPILEPSY WITH MYOCLONIC ABSENCES
Tassinari Syndrome
• Rhythmic myoclonic jerks of the shoulders and arms with tonic abduction that results in progressive lifting of the
arms during the seizure.
• The myoclonic jerks are typically bilateral but may be unilateral or asymmetric.
• Perioral myoclonias and rhythmic jerks of the head and legs may occur.
• Seizures last 10-60 seconds and typically occur daily.
• Level of awareness varies from complete loss of awareness to retained awareness.
• onset of seizures between 1 to 12 years of age (peak 7 years).
• Seizures are often difficult to treat and may continue into adulthood.
• Both sexes are affected, with a male predominance (70%).
• Cognitive impairement may be present.

66. EPILEPSY WITH MYOCLONIC ABSENCES
Tassinari Syndrome

67. Myoclonic Atonic Epilepsy
(Doose Syndrome)
• A myoclonic-atonic seizure is a myoclonic seizure followed by an atonic seizure. Sometimes a series of
myoclonic jerks occurs prior to the atonia.
• The head and limbs are affected, typically resulting in rapid fall.
• The myoclonic jerk may be subtle.
• onset between 6 months and 6 years of age (peak 2 to 4 years).
• In two thirds of children febrile seizures and generalized tonic-clonic seizures precede the onset of myoclonic-
atonic and atonic seizures.
• Both sexes are affected, with a male predominance (ratio 2:1).
• Development and cognition is typically normal, however impairments may develop at or after seizure onset.

68. Myoclonic Atonic Epilepsy
(Doose Syndrome)

69. Myoclonic Atonic Epilepsy
(Doose Syndrome)
The myoclonic component is associated with a generalized spike or polyspike.
The atonic component is associated with the aftergoing high voltage slow wave.

70. LENNOX GASTAUT SYNDROME
• This syndrome is characterized by the presence multiple types of intractable seizures (in particular tonic seizures in sleep,
but atonic and atypical absence seizures also occur), cognitive and behavioral impairments
• onset of seizures from age 1 to 7 years (peak 3 to 5 years).
• Both sexes are affected.
• Antecedent, birth and neonatal history may be normal or there may be a history related to a structural brain
abnormality (developmental or acquired).
• Neurological exam and head circumference may be normal or may reflect underlying structural brain abnormality, if
present.
• Development and cognition prior to presentation is usually abnormal, but occasionally onset may occur in an otherwise
normally developing child.
• Subsequent developmental stagnation or regression is typical after the onset of seizures.

71. LENNOX GASTAUT SYNDROME
• Around 10-30% of cases of Lennox Gastaut syndrome evolve from earlier
onset epilepsy syndromes, including West and Ohtahara syndromes.

72. LANDAU KLEFFNER SYNDROME
• Auditory Agnosia + Acquired aphasia in a child with normal previous development and cognition.
• Children become progressively unable to comprehend spoken word, cease to understand when spoken to
and to respond verbally.
• Seizures may not occur in all cases, and when present are infrequent and self-limiting.
• there is a high risk of significant residual language impairment.
• onset between the ages of 2 and 8 years (peak 5 to 7 years), or rarely later.
• The initial presentation may be with progressive aphasia (40%), seizures or both.
• Both sexes are affected.
• Language impairment typically fluctuates.
• Seizures and EEG abnormality resolve with age in most cases, however residual language impairment is
seen in the majority (>80%) and may be severe (especially if onset is earlier).

73. LANDAU KLEFFNER SYNDROME
The EEG abnormality is markedly enhanced by sleep deprivation and in sleep.
It is typical to see continuous bilateral spike-and-wave in slow sleep at some time in the
course of the disease

74. EPILEPTIC ENCEPHALOPATHY WITH CONTINUOUS
SPIKE-AND-WAVE DURING SLEEP
• characterized by continuous spike-and-wave during sleep, seizures and progressive decline in cognitive,
behavioral and psychiatric functioning.
• Childhood epilepsy with centrotemporal spikes, atypical childhood epilepsy with centrotemporal spikes,
epileptic encephalopathy with continuous spike-and-wave during sleep and Landau Kleffner
syndrome are syndromes that have in common certain EEG features, with variable severity of focal
seizures and neurocognitive impairment.
• onset of seizures between 2 and 12 years of age (peak 4-5 years), with epileptic encephalopathy with
continuous spike-and-wave during sleep developing 1-2 years after seizure onset.
• Both sexes are affected.
• cardinal symptom of this syndrome is progressive decline in cognitive, behavioral and psychiatric
functioning

75. EPILEPTIC ENCEPHALOPATHY WITH CONTINUOUS
SPIKE-AND-WAVE DURING SLEEP
continuous slow (typically 1.5-2Hz) spike-and-wave is seen in slow sleep and is seen diffusely, but may
fragment and occur focally (typically frontally) or multifocally. Some authors provide percentages of
slow wave sleep that must be occupied by continuous spike-and-wave e.g. >50% or >85%.

76. Adult Epilepsy Syndromes

77. JUVENILE ABSENCE EPILEPSY
• characterized by absence seizures that are not very frequent in an otherwise normal adolescent or
adult. Generalized tonic-clonic seizures typically also occur.
• With absence seizures in a child aged between 8 and 12 years, a diagnosis of juvenile absence epilepsy
or childhood absence epilepsy depends on the frequency of the absence seizures.
• Treatment is usually required for life.
• Both males and females are affected.
• Antecedent, birth and neonatal history is normal.
• Neurological examination is normal.
• Development and cognition prior to presentation are typically normal.
• Attention deficit hyperactivity disorder and learning difficulties may also occur.
• A previous history of febrile seizures is seen occasionally.

78. JUVENILE ABSENCE EPILEPSY

79. Juvenile Myoclonic Epilepsy
• is one of the most common genetic/idiopathic generalized epilepsies and is characterized by
myoclonic and generalized tonic clonic seizures in an otherwise normal adolescent or adult.
• onset between 8 to 25 years of age.
• A small number (approximately 5%) of cases evolve into this syndrome from childhood absence
epilepsy.
• Both males and females are equally affected.
• Antecedent and birth history is normal.
• Development and cognition are typically normal.
• Neurological examination and head size are normal.
• A history of febrile seizures is seen in 5-10%.

80. EPILEPSY WITH GENERALIZED TONIC-CLONIC
SEIZURES ALONE
• a common genetic/idiopathic generalized epilepsy. Individuals have infrequent generalized tonic-clonic
seizures from the second decade of life, typically provoked by sleep deprivation.
• between the ages of 5 to 40 years (peak 11-23 years, 80% of cases have their first tonic-clonic in the
second decade).
• Seizures may be frequent, with one fifth of cases having more than one seizure per month prior to
treatment.
• Treatment is required for life. Sleep deprivation, fatigue and alcohol lower threshold for seizures.
• Neurological examination is normal.
• Development and cognition is typically normal.

81. Juvenile Myoclonic Epilepsy

82. Etiology of Epilepsy
•Structural
•Metabolic
•Infectious
•Immune
•Genetic
•Unknown

83. Etiology of Epilepsy
Structural :
-Most patients with epilepsy require a high-resolution epilepsy- protocol brain MRI to assess the
possibility of a structural etiology.
-An exception can be made in patients with a convincing history and classical EEG findings of an
idiopathic generalized epilepsy.
-The presence of a resectable, epileptogenic lesion should trigger a surgical evaluation in patients
with medication-resistant epilepsy.
-In patients with intractable focal epilepsy and a normal MRI >>> a fludeoxyglucose positron
emission tomography (FDG-PET) scan is useful in looking for a hypometabolic region.

84. Etiology of Epilepsy
METABOLIC :
-an Epileptic encephalopathy + Seizures + Severe cognitive, sensory and/or Motor impairement.
Clues:
ü arising at an early age,
üoften refractory to antiepileptic drugs
ü severe cognitive, sensory and /or motor impairement
ü The presence of other neurologic abnormalities, such as movement disorders and ataxia, systemic
involvement
üparental consanguinity, and a positive family history

85. Etiology of Epilepsy
• METABOLIC :
General exam:
üdysmorphic features and an abnormal head circumference.
üSkin and hair abnormalities >>>Menkes syndrome or a biotinidase deficiency.
üA formal ophthalmologic evaluation is essential in identifying signs of pigmentary retinopathy
>>>(neuronal ceroid lipofuscinosis, mitochondrial disorders),
ümacular cherry-red spots >>>(gangliosidosis, Niemann-Pick disease)
ü lens dislocation >>>(sulfite oxidase deficiency)
ücataracts >>>(serine biosynthesis defects).

88. Etiology of Epilepsy
•Infectious :
Infections trigger not only acute symptomatic seizures during the initial infection but may also lead to
late seizures remote from the initial infection onset and its resolution that are instead consistent with
epilepsy
-Neurocysticercosis
-Viral encephalitis: herpes simplex type 1 , CMV , influenza B, varicella, measles, mumps, rubella, and
West Nile virus, Zika virus
-Bacterial meningitis -Fungal infection -Toxoplasmosis -Malaria -HIV

89. Etiology of Epilepsy
• Inflammatory :
autoimmune antibody syndromes are recognized as a
cause of epilepsy .
Antinuclear and Cytoplasmic Antibodies :
◆ Antineuronal nuclear antibody type 1 (ANNA-1)
(anti-Hu)
◆ Antineuronal nuclear antibody type 2 (ANNA-2)
(anti-Ri)
◆ Antineuronal nuclear antibody type 3 (ANNA-3)
◆ Antiglial neuronal antibody type 1 (AGNA) (SOX1)
◆ Purkinje cell antigen type 1 (PCA-1) (anti-Yo)
◆ Purkinje cell antigen type 2 (PCA-2)
◆ Purkinje cell antigen type Tr (PCA-Tr)
◆ Collapsin response mediator protein-5 (CRMP-5) (anti-CV2)
◆ Amphiphysin
◆ Glutamic acid decarboxylase 65 (GAD65)

90. Etiology of Epilepsy
Inflammatory :
Plasma Membrane Antibodies:
◆ N-methyl-D-aspartate (NMDA) receptor
◆ Voltage-gated potassium channel (VGKC) complex
◆ Leucine-rich glioma inactivated 1 (LGI1)
◆ Contactin-associated protein-like 2 (Caspr2)
◆ α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor
◆ γ-Aminobutyric acid (GABA)-B receptor
◆ P/Q and N-type calcium channel
◆ Neuronal ganglionic AChR
◆ IgLON5 neuronal cell surface protein

92. Inflammatory:
ANTI-NMDA RECEPTOR ENCEPHALITIS:
• Antibodies are directed against the NR1 subunit of the NMDA receptor. Clinical manifestations typically include:
• A prodrome, this may last several weeks, symptoms include fever, headache, nausea, vomiting and diarrhea
• A symptomatic phase, symptoms may include all of the following:
• Psychiatric and behavioral symptoms: anxiety, bizarre behavior, delirium, paranoia
• Insomnia or hypersomnia
• Altered level of consciousness
• Seizures (focal or generalized)
• Movement disorders: oral-motor dyskinesias, choreiform movements
• Hypoventilation
• Autonomic instability: incontinence, tachycardia, hypertension, hyperthermia

93. ANTI-NMDA RECEPTOR ENCEPHALITIS:
CSF :
may show lymptocytic pleocytosis, elevated protein, positive oligoclonal bands.
MRI: is abnormal in a third of cases with cortical/subcortical hyperintensities
commonly seen.
EEG : usually shows diffuse slowing and may show extreme delta brush pattern.
• +ve NMDA receptor antibody in CSF.
• In women the risk of ovarian teratoma is high and this should be excluded.

94. ANTI-NMDA RECEPTOR ENCEPHALITIS

95. ANTI-NMDA RECEPTOR ENCEPHALITIS

97. Dr / Souhel najjar

98. Limbic Encephalitis
Anti-Hu encephalitis. A 68-year-old man with chronic obstructive pulmonary disease presented with gradually worsening memory
deficits and confusion, with subclinical seizures. MR imaging of the brain demonstrates T2-FLAIR hyperintensity and mild expansion
in the right medial temporal lobe (A), right insular cortex (not shown), and left dorsal thalamus (not shown), without restricted
diffusion (not shown) or postcontrast enhancement (not shown). FDG-PET of the brain demonstrates a hypermetabolic focus
within the right medial temporal lobe lesion (B). PET of the body demonstrates a hypermetabolic focus in the left lung (E),
consistent with biopsy-proved small-cell lung cancer. The patient was in remission following treatment with intravenous
immunoglobulin infusions, oral steroids, and chemotherapy, but he presented approximately 2.5 years later with worsening
memory decline. MR imaging at that time (C and D) shows new T2-FLAIR hyperintensity in the left medial temporal lobe (white
arrow) with volume loss within the right medial temporal lobe (white arrowhead). An old right occipital lobe infarct is also
incidentally noted.

99. ADEM

100. Bickerstaff’s brainstem encephalitis

101. Bickerstaff’s brainstem encephalitis

102. Hashimoto’s encephalopathy
A 41-year-old woman presented with gradually worsening headaches and memory impairment
without the development of psychosis or seizures. MR imaging of the brain (time, 0)
demonstrates T2-FLAIR hyperintensity in the inferior left temporal lobe (A) without evidence of
restricted diffusion (B and C). MR imaging of the brain (time, 21 days) demonstrates
enlargement of the lesion on T2-FLAIR (not shown) without postcontrast enhancement (D). MR
imaging of the brain (time, 3 months) demonstrates resolution of the prior lesion (not shown)
but development of similar T2-FLAIR hyperintensity in the right frontoparietal junction (E). A
subsequent scan at approximately 5 months shows near-complete resolution of that lesion
with a new T2-FLAIR hyperintense lesion more posteriorly (F). A follow-up scan (G and H) nearly
1 year from onset shows complete resolution of the imaging abnormalities.

103. Etiology of Epilepsy
GENETIC :
-Only approximately 30% of epilepsies are acquired, and the remaining 70% are likely caused by one or more genetic factors.
-The genetics of epilepsies follow a complex pattern, and most genetically determined epilepsies have a polygenic basis with
several susceptibility genes contributing to the disease.
-Next-generation sequencing technology has revolutionized gene discovery in epilepsy and many other disorders.
• The clinical neurologist should be familiar with a small group of genetic epilepsies that present with a rather distinct clinical
phenotype and if clinically indicated can be evaluated with commercially available gene panels. Notable genetic epilepsies
include the autosomal dominant focal epilepsies:
vAutosomal dominant temporal lobe epilepsy
vAutosomal dominant nocturnal frontal lobe epilepsy
vFamilial focal epilepsy with variable foci

104. Etiology of Epilepsy
• Genetic:
Autosomal dominant temporal lobe epilepsy:
is associated with mutations in the LGI1 (30%) and RELN gene and has a 55% to 78% penetrance .
Autosomal dominant nocturnal frontal lobe epilepsy :
is associated with neuronal nicotinic acetylcholine receptor mutations, which are seen in 20% of patients with this disorder.
Familial focal epilepsy with variable foci :
is associated with mutations in the DEPDC5, NPRL2, and NPRL3 genes, all part of the guanosine triphosphatase (GTPase)–
activating protein activity toward Rag (GATOR) complex, accounting for at least 10% of familial frontal lobe epilepsies. Patients
show variable foci and a 50% to 80% penetrance. Onset is variable from 1 month to 51 years of age with an average of 12 years.
Long periods of remission in the teen/adult years are noted.

105. Etiology of Epilepsy
• Genetic:
-It is worthwhile to be familiar with glucose transporter type 1 (GLUT1) deficiency
syndromes associated with SLC2A1 gene mutation given the excellent response to dietary
treatment and the recent discovery of milder, later-onset variants.
• Genetic counseling for a specific epilepsy syndrome can be straightforward in patients
with a 100% penetrant syndrome but complicated in situations of incomplete
penetrance and de novo mutations (eg, Dravet syndrome) and should be performed
• with the help of a genetic counselor.

107. Epilepsy Comorbidities
• Epilepsy presents with a bidirectional relationship with other neurologic (eg, stroke, migraine,
dementia, traumatic brain injury) and psychiatric (eg, depression and anxiety) comorbidities.
• Several Diseases including depression, anxiety, dementia, migraine, heart disease, peptic ulcers, and
arthritis, are up to 8 times more common in people with epilepsy than in the general Population.
• The prevalence of comorbidities persists even in patients in seizure remission, and patients with
inactive epilepsy remain at risk of premature mortality, suggesting a systemic component involved in
the etiology of epilepsy.

108. • Recognizing the cause of a first seizure and identifying the etiology of epilepsy are essential
for management.
• A systematic approach to patients who present with a first seizure helps distinguish between
an acute symptomatic seizure, a provoked or unprovoked seizure, and potential mimickers.
• Routine testing with EEG and MRI may reveal a predisposition for further seizures and help to
establish the underlying epilepsy syndrome
• An acquired etiology can be identified in 30% of patients with established epilepsy
• The remaining 70% of patients have a presumably genetic etiology.
Home message

109. Email: m.a.tarek91@gmail.com
Mohamed A. Tarek MohammedAhmadTarek